Several short peptide (<20 residues) can adopt a-helical structure in aqueous solution. We are analyzing the factors which control the helical structure of these peptides, including the intrinsic helix-forming tendencies of different amino acids and specific stabilizing interactions between side chains. These interactions include electrostatic interactions between specific side chains and between side chains and the a-helix macro-dipole as well as hydrophobic interactions between nonpolar side chains. Our basic host peptide is comprised primarily of alanine with either lysine or glutamine added to afford water solubility. The alanine host peptide is helical because of the high intrinsic helix forming tendency of alanine. We make specific substitutions into this host peptide in order to investigate the helix propensities of other residues, or to make measurements of specific interactions between side chains. The data are analyzed with classical helix-coil transition theory which allows us to quantitate the effects of single replacements or specific interactions on the stability of the a-helical peptide.